WORKLIST ENTRIES (1): WNT3PROTEIN View alignment Wnt-3 protein signature Type of fingerprint: COMPOUND with 3 elements Links: PRINTS; PR01349 WNTPROTEIN PRINTS; PR01841 WNT1PROTEIN; PR01842 WNT2PROTEIN; PR01844 WNT4PROTEIN PRINTS; PR01845 WNT6PROTEIN; PR01891 WNT7PROTEIN; PR01892 WNT8PROTEIN PRINTS; PR01893 WNT10PROTEIN; PR01894 WNT14PROTEIN; PR01895 WNT16PROTEIN MIM; 165330 Creation date 06-JAN-2003 1. WODARZ, A. AND NUSSE, R. Mechanisms of Wnt signal transduction. ANNU.REV.CELL DEV.BIOL. 14 59-88 (1998). 2. BEJSOVEC, A. Signal transduction: Wnt signalling shows its versatility. CURR.BIOL. 9 R684-R687 (1999). 3. DE FERRARI, G.V. AND INESTROSA, N.C. Wnt signaling function in Alzheimer's disease. BRAIN RES.BRAIN RES.REV. 33 1-12 (2000). 4. SEMENOV, M.V. AND SNYDER, M. Human dishevelled genes constitute a DHR-containing multigene family. GENOMICS 42 302-310 (1997). 5. PEIFER, M. AND POLAKIS, P. Wnt signalling in oncogenesis and embryogenesis - a look outside the nucleus. SCIENCE 287 1606-1609 (2000). 6. MOON, R.T. An introduction to non-canonical Wnt and Frizzled signaling. SEMIN.CELL DEV.BIOL. 13 215 (2002). 7. ROELINK, H., WAGENAAR, E., SILVA, S.L.D. AND NUSSE, R. Wnt-3, a gene activated by proviral insertion in mouse mammary tumors, is homologous to int-1/Wnt-1 and is normally expressed in mouse embryos and adult brain. PROC.NATL.ACAD.SCI.U.S.A. 87 4519-4523 (1990). 8. ROELINK, H., WANG, J., BLACK, D.M., SOLOMON, E. AND NUSSE, R. Molecular cloning and chromosomal localization to 17q21 of the human WNT3 gene. GENOMICS 17 790-792 (1993). Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) . It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals . Wnt signalling has been implicated in tumorigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease [3,4]. Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in development . More recently, however, several non-canonical Wnt signalling pathways have been elucidated that act independently of B-catenin . Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of Wnts as they are notoriously insoluble; in terms of primary structure, the family is characterised by a signal sequence and an almost invariant pattern of 23-24 conserved cysteines . Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes. The Wnt-3 gene was first identified in mouse in 1987, where it was found to be expressed during embryogenesis and in adult brain. Insertion of proviral DNA from mouse mammary tumour virus (MMTV) occurs at the mouse Wnt-3 locus, leading to activation of the gene . However, the human Wnt-3 gene was not found to be amplified or rearranged in breast cancer tissues . WNT3PROTEIN is a 3-element fingerprint that provides a signature for Wnt-3 proteins. The fingerprint was derived from an initial alignment of 2 sequences: the motifs were drawn from conserved regions spanning the C- terminal half of the alignment, focusing on those sections that characterise Wnt-3 proteins but distinguish them from related Wnt subtypes - the motifs reside between a number of highly conserved cysteines. Two iterations on SPTR40_20f were required to reach convergence, at which point a true set comprising 6 sequences was identified. A single partial match was also found, Q8WS76, a putative WNT3 protein from Branchiostoma floridae (Florida lancelet) that fails to make a significant match with motif 2. SUMMARY INFORMATION 6 codes involving 3 elements 1 codes involving 2 elements COMPOSITE FINGERPRINT INDEX 3| 6 6 6 2| 1 0 1 --+---------------- | 1 2 3 True positives.. WNT3_HUMAN WNT3_MOUSE Q9PWH1 WN3A_XENLA WN3A_MOUSE Q969P2 Subfamily: Codes involving 2 elements Subfamily True positives.. Q8WS76 PROTEIN TITLES WNT3_HUMAN WNT-3 proto-oncogene protein precursor - Homo sapiens (Human WNT3_MOUSE WNT-3 proto-oncogene protein precursor - Mus musculus (Mouse Q9PWH1 WNT-3A - Gallus gallus (Chicken). WN3A_XENLA WNT-3A protein precursor (XWNT-3A) - Xenopus laevis (African WN3A_MOUSE WNT-3A protein precursor - Mus musculus (Mouse). Q969P2 CDNA FLJ31716 FIS, CLONE NT2RI2006565, HIGHLY SIMILAR TO WNT Q8WS76 SECRETED GLYCOPROTEIN WNT3 - Branchiostoma floridae (Florida
SCAN HISTORY SPTR40_20f 2 300 NSINGLE INITIAL MOTIF SETS WNT3PROTEIN1 Length of motif = 10 Motif number = 1 Wnt-3 protein motif I - 1 PCODE ST INT SHHKGPPGEG WNT3_HUMAN 143 143 SHHKGPPGEG WNT3_MOUSE 143 143 WNT3PROTEIN2 Length of motif = 13 Motif number = 2 Wnt-3 protein motif II - 1 PCODE ST INT ADARENRPDARSA WNT3_HUMAN 173 20 ADARENRPDARSA WNT3_MOUSE 173 20 WNT3PROTEIN3 Length of motif = 12 Motif number = 3 Wnt-3 protein motif III - 1 PCODE ST INT GHNTRTEKRKEK WNT3_HUMAN 318 132 GHNTRTEKRKEK WNT3_MOUSE 318 132 FINAL MOTIF SETS WNT3PROTEIN1 Length of motif = 10 Motif number = 1 Wnt-3 protein motif I - 2 PCODE ST INT SHHKGPPGEG WNT3_HUMAN 143 143 SHHKGPPGEG WNT3_MOUSE 143 143 TRHKGSPGEG Q9PWH1 164 164 THHKGPPGEG WN3A_XENLA 140 140 SRLQGSPGEG WN3A_MOUSE 140 140 SRHQGSPGKG Q969P2 140 140 WNT3PROTEIN2 Length of motif = 13 Motif number = 2 Wnt-3 protein motif II - 2 PCODE ST INT ADARENRPDARSA WNT3_HUMAN 173 20 ADARENRPDARSA WNT3_MOUSE 173 20 ADARENRPDARSA Q9PWH1 194 20 ADARENRPDARSA WN3A_XENLA 170 20 ADARENRPDARSA WN3A_MOUSE 170 20 ADARENRPDARSA Q969P2 170 20 WNT3PROTEIN3 Length of motif = 12 Motif number = 3 Wnt-3 protein motif III - 2 PCODE ST INT GHNTRTEKRKEK WNT3_HUMAN 318 132 GHNTRTEKRKEK WNT3_MOUSE 318 132 GHNTRTEKRKEK Q9PWH1 339 132 GQNTRTEKRKEK WN3A_XENLA 315 132 GHNARTERRREK WN3A_MOUSE 315 132 GHNARAERRREK Q969P2 315 132
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